Because obesity affects the cellular immune response to infections, we aimed to investigate whether high body mass index (BMI) in young adulthood and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels interact with regard to MS risk. We also aimed at exploring potential 3-way interactions between BMI at age 20 years, aspects of Epstein-Barr virus (EBV) infection (high EBNA-1 antibody levels and infectious mononucleosis [IM] history, respectively) and the human leukocyte antigen (HLA)-DRB1*15:01 allele.
Using Swedish population-based case-control studies (5,460 cases and 7,275 controls), we assessed MS risk in relation to interactions between overweight/obesity at age 20 years, IM history, EBNA-1 levels, and HLA-DRB1*15:01 status by calculating ORs with 95% CIs using logistic regression. Potential interactions were evaluated on the additive scale.
Overweight/obesity, compared with normal weight, interacted significantly with high (>50th percentile) EBNA-1 antibody levels (attributable proportion due to interaction 0.2, 95% CI 0.1–0.4). The strength of the interaction increased with higher category of EBNA-1 antibody levels. Furthermore, 3-way interactions were present between HLA-DRB1*15:01, overweight/obesity at age 20 years, and each aspect of EBV infection.
With regard to MS risk, overweight/obesity in young adulthood acts synergistically with both aspects of EBV infection, predominantly among those with a genetic susceptibility to the disease. The obese state both induces a chronic immune-mediated inflammation and affects the cellular immune response to infections, which may contribute to explain our findings.